An Open-Label, Bayesian Adaptive Phase II Clinical Study in HR+/HER2- Advanced Breast Cancer After Progression on Standard Therapy

ConditionBreast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorFudan University

About this trial

This is a prospective, Phase II, open-label, two-arm parallel study evaluating the efficacy and safety of combined treatment (L-Ornithine L-Aspartate, N-Acetylcysteine) with CDK4/6 inhibitors and Fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer (ABC) who have progressed on prior standard therapy including CDK4/6 inhibitors and endocrine therapy.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Women aged ≥ 18 years old.

Patients with histologically confirmed HR+/HER2- invasive breast cancer (specific definition: ER > 10% tumor cell positivity by immunohistochemistry is defined as ER positive, PR positive, PR > 10% tumor cell positivity is defined as PR positive; HER2 0 - 1+ or HER2 ++ but negative by FISH without amplification is defined as HER2 negative).

Patients with HR+/HER2- advanced breast cancer who have experienced disease progression after receiving systemic therapy including CDK4/6 inhibitors and endocrine therapy.

Patients whom the investigator judges to be suitable for continued endocrine therapy

Disqualifiers

Patients who have received radiotherapy (except for palliative reasons), chemotherapy, immunotherapy, or bisphosphonates (except for bone metastases) within 3 weeks prior to treatment.

Patients with uncontrolled central nervous system metastases (defined as symptomatic or requiring the use of corticosteroids or mannitol to control symptoms).

Patients with a history of clinically important or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction within the past 6 months, or ventricular arrhythmia.

Patients with ongoing ARs ≥ Grade 1 due to prior therapy. Exception to this is alopecia or those that, in the opinion of the investigator, should not be excluded. Such cases should be clearly documented in the investigator's notes.

Trial design

Design model

Parallel

Treatments tested in this trial

  • L-Ornithine L-Aspartate

    Drug

    3g orally three times daily

  • CDK4/6 inhibitor

    Drug

    at the physician's choice

  • Fulvestrant

    Drug

    500mg IM on Days 1 \& 15 of Cycle 1, then Day 1 of subsequent cycles

  • N-Acetylcysteine (NAC) Treatment

    Drug

    600mg orally twice daily

  • Pioglitazone (PIO)

    Drug

    30mg orally once daily

  • PARP inhibitor

    Drug

    at the physician's choice

Treatment groups

60 Participants
are divided into 3 treatment groups
Group A: CDK4/6 inhibitor + Fulvestrant + L-Ornithine L-AspartateExperimental treatment 3 interventions
Group B: CDK4/6 inhibitor + Fulvestrant + N-AcetylcysteineExperimental treatment 3 interventions
Group C: PARP inhibitor + Fulvestrant + PioglitazoneExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Objective Response Rate (ORR)

Time frame
Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

Secondary outcomes

1

Disease Control Rate (DCR)

Time frame
Baseline through end of study, assessed up to 6 months
2

Progression Free Survival (PFS)

Time frame
Randomization to death from any cause, through the end of study, assessed up to 6 months
3

Safety and treatment-related AEs (assessed by CTCAE v5.0)

The total count and percentage of participants experiencing treatment-related AEs, classified by severity (Grades 1-5) according to CTCAE v5.0

Time frame
Randomization to death from any cause, through the end of study, assessed up to 12 months
4

Biomarker analysis

Pre- and post-treatment samples (tumor tissue, blood, and feces) will be analyzed for blood ammonia levels, ammonia-related genes, cell functions, and microbes to predict therapy response

Time frame
Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

Other outcomes

Sponsors and contacts

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